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Trial registered on ANZCTR


Registration number
ACTRN12617001583336
Ethics application status
Approved
Date submitted
13/11/2017
Date registered
27/11/2017
Date last updated
12/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase 1, randomized, double-blind, placebo-controlled, sequential-panel, ascending single-dose study to evaluate the safety, tolerability, and pharmacokinetics of intravenous CMX-020 in healthy male and female subjects
Scientific title
A phase 1, randomized, double-blind, placebo-controlled, sequential-panel, ascending single-dose study to evaluate the safety, tolerability, and pharmacokinetics of intravenous CMX-020 in healthy male and female subjects
Secondary ID [1] 293278 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pain Control 305353 0
Condition category
Condition code
Anaesthesiology 304636 304636 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Up to six (6) dose levels with approximately two weeks between the dosing of each group.

In total of 6 cohorts:
Cohort 1: CMX-020 drug- 0.02 (mg/kg) - Single Intravenous infusion over 15 min
Cohort 2: CMX-020 drug- 0.04 (mg/kg) - Single Intravenous infusion over 15 min
Cohort 3: CMX-020 drug- 0.08 (mg/kg) - Single Intravenous infusion over 15 min
Cohort 4: CMX-020 drug- 0.16 (mg/kg) - Single Intravenous infusion over 15 min
Cohort 5: CMX-020 drug- 0.24 (mg/kg) - Single Intravenous infusion over 15 min
Cohort 6: CMX-020 drug- 0.32 (mg/kg) - Single Intravenous infusion over 15 min

Each escalating dose group will consist of 8 subjects; 6 will be randomized to receive a single dose of CMX-020, and 2 will be randomized to receive a single dose of placebo.
Intervention code [1] 299535 0
Treatment: Drugs
Comparator / control treatment
This is a Phase I, randomized, double-blind, placebo-controlled, sequential-panel, ascending single-dose, single-center study.

Each dose group will consist of 8 subjects; 6 will be randomized to receive a single dose of CMX-020, and 2 will be randomized to receive a single dose of placebo.

Placbo contains 20 mL of 20% hydroxypropyl-ß-cyclodextrin in 35% phosphate buffered saline-65% water solution in 25 mL glass vials.
Control group
Placebo

Outcomes
Primary outcome [1] 303863 0
To evaluate the safety and tolerability of escalating single doses of CMX-020 administered as a 15-minute intravenous infusion to healthy male and female subjects

Safety Endpoints:
•Continuous blood pressure monitoring
• 12-lead ECG pre and post-dose
• Continuous EEG monitoring
• Vital sign (blood pressure, pulse, respiration rate, temperature) monitoring
• Continuous oxygen saturation monitoring
• Drug Feel and Drug Likeability Ratings (VAS)
• Adverse event reporting
Timepoint [1] 303863 0
•Continuous blood pressure monitoring:
Blood pressure will be recorded continuously by Nexfin® device beginning 10 minutes prior to the start of infusion continuing until 30 minutes after the start of infusion.

•12-lead ECG pre and post-dose:
ECGs will be recorded at least one hour before dosing on Day 1 (baseline recording), at 7, 16, 46 minutes and at 2:01 post-infusion start, and at the Post-Treatment Visit (Day 4) as part of the study exit exam.

• Continuous EEG monitoring:
A single lead EEG recording will begin 15 minutes prior to the start of infusion and continue until 35 minutes after the start of infusion.

• Vital sign (blood pressure, pulse, respiration rate, temperature) monitoring:
Vital signs will be recorded at Screening and at check-in. On Day 1 respiratory rate, , and pulse rate will be recorded 11 minutes prior to the infusion, and 1, 3, 6, 11, 16, 21, and 31 minutes and at 1:02, 1:32, 2:02, 2:32, 3:02, 3:32 and 4:02 after infusion start. Blood pressure will be recorded continuously by Nexfin® device beginning 10 minutes prior to the start of infusion continuing until 30 minutes after the start of infusion. Blood pressure measurement from cuff will be taken at 11 minutes prior to the start of infusion and at 0:31, 1:02, 1:32, 2:02, 2:32, 3:02, 3:32 and 4:02 after infusion start. Tympanic temperature will also be measured at 11 minutes prior to and 31 minutes after the start of infusion.

• Continuous oxygen saturation monitoring:
Pulse oximetry readings will be recorded at -11 minutes prior to infusion, and 6, 11, 21, and 31 minutes, and at 1:02, 1:32, and 2:02 after initiation of infusion (+/- 1 min), and any time the oxygen saturation drops below 90%.

• Drug Feel and Drug Likeability Ratings (VAS):
Drug Feel and Drug Likeability VAS Rating completed by the subject at 6, 14, 32, and 61 minutes (+/- 1 min) post-infusion start.

• Adverse event reporting: Treatment Day 1, Post-treatment Day 4
Primary outcome [2] 303864 0
To determine the Maximum Tolerated Dose (MTD) of
CMX-020 administered as a 15-minute intravenous infusion to healthy male and female subjects.

If two or more subjects in a given dose panel experience the same or different adverse events or changes in clinical laboratory evaluations which are Grade equal to or greater than 3, exceed the safety limits for blood pressure, pulse, or oxygen saturation or experience any combination of the above potentially dose limiting toxicities at any time during the study, the treatment randomization will be unblinded to determine if the subjects received active drug or placebo. If unblinding reveals that two or more subjects experiencing any of these dose limiting toxicities in a given panel received CMX-020, dose escalation will stop and the prior dose will be considered the Maximum Tolerated Dose (MTD).
Timepoint [2] 303864 0
At each dose level prior proceeding to the next dose level
Secondary outcome [1] 340311 0
To describe the single-dose pharmacokinetics of escalating doses of CMX-020 administered as a 15-minute intravenous infusion to healthy male and female subjects.

Pharmacokinetic parameters in plasma will be computed for CMX-020 and its metabolite, DB-130, using noncompartmental methods. Pharmacokinetic parameters (Cmax, Tmax, AUC(0-tlqc), AUC(0-inf), t1/2, lambdaz , CL, Vd, MRT) will be summarized for each dose group using descriptive statistics.
Analysis of covariance (ANCOVA) will be performed for Tmax and lambdaz, and natural logarithms of dose-normalized Cmax, dose-normalized AUCs, and MRT with dose and body weight as a covariate in the model, for CMX-020 and DB-130. Test for dose-proportionality will also be performed.
Timepoint [1] 340311 0
Blood samples for pharmacokinetic analysis of CMX-020 and DB-130 metabolite will be collected on Treatment Day 1 at the following times: -30 minutes pre-infusion, and 2, 5, 10, 15, 17, 20, 25, 30, and 45 minutes and at 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 after the start of the infusion.

Eligibility
Key inclusion criteria
To qualify for enrollment in this study, the subject must satisfy the following inclusion criteria:
• Healthy adult male or adult female between the ages of 18-50 years in good physical health.
• Of non-childbearing potential or using an acceptable form of contraception
• Weigh at least 50 kg, and no more than 90and have a body mass index (BMI) between 18 and 32 kg/m2
• Clinical laboratory results (including clinical chemistry, hematology, and urinalysis) within the reference range for the testing laboratory
• Negative tox, hepatitis and HIV screens
• Creatinine clearance of at least 70 mL/min
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Any subject who meets any of the following criteria will not qualify for entry into the study:
• History of drug abuse, cancer, liver disease, seizure, metabolic disease or head trauma
• Systolic blood pressure > 140 mm Hg or < 90 mm Hg, or diastolic blood pressure > 90 mm Hg during the Pretreatment Screening or Baseline/Check-in Periods
• Pulse > 100 beats/minute or < 50 beats/minute during the Pretreatment Screening or Baseline/Check-in Periods
• Pulse oximetry values <95% on room air; temperature <35.8°C and >37.5°C
• Clinically significant abnormal ECG at Pretreatment Screening or Baseline/Check-in Periods or history of Long QT Syndrome
• Clinical laboratory values within the normal limits as defined by the clinical laboratory, unless the investigator decides that out-of-range values are not clinically significant
• Recent use of alcohol, tobacco, prescription or OTC medications

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
29/11/2017
Actual
10/01/2018
Date of last participant enrolment
Anticipated
Actual
14/06/2018
Date of last data collection
Anticipated
Actual
21/06/2018
Sample size
Target
48
Accrual to date
Final
64
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 297905 0
Commercial sector/Industry
Name [1] 297905 0
Cytometix Inc
Country [1] 297905 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Cytometix Inc
Address
9445 Fairway Circle
Bayside, WI-53217 USA
Country
United States of America
Secondary sponsor category [1] 296961 0
None
Name [1] 296961 0
Address [1] 296961 0
Country [1] 296961 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298955 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 298955 0
Level 4, Women’s Health Centre
Royal Adelaide Hospital
North Terrace
Adelaide, South Australia, 5000
Ethics committee country [1] 298955 0
Australia
Date submitted for ethics approval [1] 298955 0
20/01/2017
Approval date [1] 298955 0
04/03/2017
Ethics approval number [1] 298955 0

Summary
Brief summary
This is a Phase I, randomized, double-blind, placebo-controlled, sequential-panel, ascending single-dose, single-center study to evaluate the safety and tolerability, and describe the pharmacokinetics of escalating single doses of CMX-020 administered as a 15-minute intravenous infusion to healthy male and female subjects.

The study population will be comprised of up to 48 healthy male and female subjects aged 18-50 years, inclusive, considered eligible on the basis of study inclusion and exclusion criteria. Each subject who meets eligibility criteria will be randomly assigned to receive CMX-020 or placebo. Each escalating dose group will consist of 8 subjects; 6 will be randomized to receive a single dose of CMX-020, and 2 will be randomized to receive a single dose of placebo. Treatment groups will be dosed in an escalating order, each dose level increased by no more than 2-fold over the previous dose level. The decision to escalate the dose will be based upon review of the safety and EEG data for all subjects in each previous dosing panel. No subject will receive more than one dose of study medication.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78778 0
Prof Guy Ludbrook
Address 78778 0
PARC Clinical Research
Level 4G,
Royal Adelaide Hospital,
Port Road, Adelaide, South Australia,
AUSTRALIA 5000
Country 78778 0
Australia
Phone 78778 0
+61 8 70741544
Fax 78778 0
Email 78778 0
[email protected]
Contact person for public queries
Name 78779 0
Guy Ludbrook
Address 78779 0
PARC Clinical Research
Level 4G,
Royal Adelaide Hospital,
Port Road, Adelaide, South Australia,
AUSTRALIA 5000
Country 78779 0
Australia
Phone 78779 0
+61 8 70741544
Fax 78779 0
Email 78779 0
[email protected]
Contact person for scientific queries
Name 78780 0
Guy Ludbrook
Address 78780 0
PARC Clinical Research
Level 4G,
Royal Adelaide Hospital,
Port Road, Adelaide, South Australia,
AUSTRALIA 500
Country 78780 0
Australia
Phone 78780 0
+61 8 70741544
Fax 78780 0
Email 78780 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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